An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis

Rigorous and systematic pre-clinical studies are necessary and essential to establish the efficacy and safety of Oriental herbs and formulas in order to transform traditional herbal practices into evidence-based medicine. Here we evaluated the anti-cancer activities of the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT), a formula of ten Oriental herbs, with a battery of in vitro and in vivo mechanism-based biomarkers involving angiogenesis, apoptosis and metastasis. The results show that KMKKT suppressed the vascular endothelial responses by inhibiting basic fibroblast growth factor (bFGF)-induced ERK1/2 phosphorylation, cell migration as well as tube formation in the human umbilical vein endothelial cell model, and decreased the hypoxia-induced HIF1α and vascular epithelial growth factor (VEGF) expression in the mouse Lewis lung carcinoma (LLC) cells in vitro, and inhibited the bFGF-induced angiogenesis in chick chorioallantoic membrane model, and in the Matrigel plugs in mice. Intraperitoneal delivery of KMKKT potently inhibited the growth of the subcutaneously inoculated LLC cells in syngenic mice. In addition, KMKKT inhibited the invasion ability of the mouse colon 26-L5 cancer cells in vitro and decreased their formation of liver metastasis when intraportally inoculated in syngenic mice. Furthermore, KMKKT suppressed the growth of the human PC-3 prostate cancer xenografts in athymic nude mice and averted the cancer-related body weight loss. The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis. Together, our data support broad-spectra in vivo anti-cancer activities of KMKKT targeting angiogenesis, apoptosis and metastasis without any adverse effect on the body weight. This formula merits serious consideration for further evaluation for the chemoprevention and treatment of cancers of multiple organ sites.
pin yin Name origin Gms %
dong gua zi Benincasa hispida (seed) China 30 17.24
ba ji Bletilla striata (root and tuber) China 15 8.62
la ya ban (shan ci gu) Tulipa edulis (stem tuber) Korea 15 8.62
ren shen Panax ginseng (root) Korea 15 8.62
chi dou Phaseolus angularis (seed) Korea 30 17.24
hu jiao mu Zanthoxylum piperitum (seed) Korea 12 6.9
bai hua bai jiang Patrinia villosa (root) China 15 8.62
huang qi Astragalus membranaceus (root) Korea 15 8.62
chao xian dang gui Angelica gigas Nakai (root) Korea 12 6.9
e jiao Asini gelatinum Korea 15 8.62

Introduction
Cancers of the lung, prostate and colorectal account for the majority of cancer mortality in the USA and in the Western countries (1). Chemotherapy using available cytotoxic anti-cancer drugs for advanced-stage malignancies in the lung and prostate offers little survival benefit (2,3). All current chemotherapy modalities have significant side effects and dose-limiting toxicities (2,3). It is now being increasingly recognised that intervening critical processes of cancer growth and development including angiogenesis and metastasis with naturally occurring herbal and phytochemical agents to achieve chemo-prevention is crucial to decreasing the morbidity and mortality of these and other cancers.

Chinese/Oriental herbal medicine has long been used for treating malignancies. Whereas single herbs are seldom used alone, herbal cocktails take advantage of synergy and interactions among a myriad of phytochemicals present in the different herbs to achieve therapeutic efficacy targeting multiple biological and pathological processes while minimising side effects. However, herbal remedies are yet to be integrated into main stream medicine due to a number of challenges, including herbal standardisation and quality control issues, safety and toxicity concerns, interactions with existing therapeutic modalities, a lack of proven efficacy by standard clinical trials and a lack of mechanistic details, to name a few (4). Rigorous in vitro and pre-clinical animal studies will be essential and necessary to evaluate their efficacy and safety before clinical trials can be contemplated for the chemoprevention and treatment of these major cancers in humans and to transform traditional herbal practices into ‘evidence-based medicine’.

Here we report the evaluation of an anti-cancer formula of ten Oriental herbs, Ka-mi-kae-kyuk-tang (KMKKT) (5), with a battery of in vitro and in vivo pre-clinical tests. In addition to tumour cell proliferation and apoptosis, we focused on angiogenesis assays because of the central importance of angiogenesis in supporting tumour growth and metastasis (6–9). Angiogenesis in embryonic development, reproduction and wound healing is tightly regulated by a balance between the angiogenic inhibitors and activators and in neoplasia, the delicate balance is tilted to favour increased angiogenesis (6–9). In terms of the angiogenic activators, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been well documented (10–12). Even though VEGF is a primary mediator of angiogenic responses, bFGF is more potent than VEGF for stimulating the vascular endothelial mitogenesis. Hence bFGF is the most often used angiogenic polypeptide for experimental studies (13) and we used it for our angiogenesis tests in the current work. Tumour growth and progression require angiogenesis because in its absence tumour growth is restricted to 1–2 mm in diameter due to the physical constraint set by simple diffusion of nutrients and oxygen (6–12). In addition, angiogenesis and vascularisation provide an important avenue for the extravasation of metastatic tumour cells to the circulation and for them to re-establish in the other organ sites. Consequently, the inhibition of neo-angiogenesis has been considered an attractive and rationale approach to cancer chemoprevention and therapy (14,15). Thus, in the present study, we focused on the anti-angiogenic effects of KMKKT for screening purposes. We tested the in vivo efficacy of this formula against three models of mouse and human solid tumour growth or metastasis. The results support the merit of this cocktail for the chemoprevention and therapy of cancers of multiple organ sites.
Source:
Lee H-J, Lee E-O, Rhee Y-H, et al. Carcinogenesis (2006) 27 (12): 2455-2463. doi: 10.1093/carcin/bgl104

References:
1. Jemal A, et al. Cancer statistics, 2005. CA Cancer J. Clin. 2005;55:10-30.
2. Petrylak D.P. The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Urology 2005;65 Suppl. 5:3-7. discussion 7–8.
3. Evans T. Chemotherapy in advanced non-small cell lung cancer. Semin. Respir. Crit. Care Med. 2005;26:304-313.
4. Buchanan DR, et al. Research-design issues in cancer-symptom-management trials using complementary and alternative medicine: lessons from the National Cancer Institute Community Clinical Oncology Program experience. J. Clin. Oncol. 2005;23:6682-6689.
5. Jiang C, et al. Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. Cancer Res. 2006;66:453-463.
6. Folkman J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 1971;285:1182-1186.
7. Folkman J, Shing Y. Angiogenesis. J. Biol. Chem. 1992;267:10931-10934.
8. Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1995;1:27-31.
9. Folkman J. Angiogenesis and apoptosis. Semin. Cancer Biol. 2003;13:159-167.
10. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996;86:353-364.
11. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-257.
12. Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat. Rev. Cancer 2003;3:401-410.
13 Chen CH, Poucher SM, Lu J, Henry PD. Fibroblast growth factor 2: from laboratory evidence to clinical application. Curr. Vasc. Pharmacol. 2004;2:33-43.
14. Madhusudan S, Harris AL. Drug inhibition of angiogenesis. Curr. Opin. Pharmacol. 2002;2:403-414.
15. Tosetti F, Ferrari N, De Flora S, Albini A. Angioprevention’: angiogenesis is a common and key target for cancer chemopreventive agents. FASEB. J. 2002;16:2-14.

You can leave a response, or trackback from your own site.

14 Responses to “An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis”

  1. A person necessarily lend a hand to make severely posts I would state. This is the first time I frequented your website page and to this point? I amazed with the analysis you made to create this actual publish amazing. Magnificent process!

  2. Thank you for the good writeup. It in reality used to be a enjoyment account it. Glance complicated to more added agreeable from you! However, how could we keep up a correspondence?

  3. Sbu says:

    not to take the drugs and get the chemo as they will only kill you and make it hdarer for natural fresh raw fruits and vegetables to help your body combat and in almost every case cure even terminal cancer.Do you have to dress it up as something else in order not to get your licence revoked?Persecuting Gerson Therapy is a big deal in the USA even if there are clinics popping up all over the world, if I got cancer it would be off to Mexico, Japan or Sweeden if I didn’t feel I could manage the diet on my own. I highly recommend the Gerson Therapy book and there are tons of resources online about it.

  4. I’m not certain where you are getting your information, however good topic. I needs to spend some time studying more or figuring out more. Thanks for excellent information I was searching for this information for my mission.

  5. All You Need To Know About Mesothelioma…

    […]An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis | ASSOCIATION OF INTEGRATIVE ONCOLOGY AND CHINESE MEDICINE(AIOCM)[…]…

  6. Awesome blog! Do you have any tips for aspiring writers? I’m hoping to start my own blog soon but I’m a little lost on everything. Would you recommend starting with a free platform like WordPress or go for a paid option? There are so many choices out there that I’m totally overwhelmed .. Any recommendations? Bless you!

  7. I just added this website to my rss reader, great stuff. Can not get enough!

  8. Thanks a lot for the helpful write-up. It is also my opinion that mesothelioma cancer has an particularly long latency period of time, which means that symptoms of the disease might not exactly emerge right until 30 to 50 years after the first exposure to asbestos fiber. Pleural mesothelioma, that’s the most common style and affects the area across the lungs, might cause shortness of breath, chest pains, plus a persistent cough, which may lead to coughing up blood.

  9. Benny Alfaro says:

    some truly prize blog posts on this site, bookmarked .

  10. Loving the information on this site, you have done outstanding job on the blog posts.

  11. I believe you have mentioned some very interesting points , appreciate it for the post.

  12. Elitarny says:

    Perfect layout! How did you get it?

  13. Marcellus Stromquist says:

    Cancer symptoms usually manifests itself as intense pain. Therefore, if you experience such pain, you need to have some medical evaluation. ‘,:.;

    Warmest regards http://www.foodsupplementdigest.com“>

Leave a Reply

You must be logged in to post a comment.