Sunday, 16 June 2019

Cucurbitacin B (CuB) Isolated from Cucumbers (Cucumis sativus), a Natural Antiangiogenic and Antimetastatic Potential Bioactve Compound

By Kyle J. Norton

Metastasis is a process in which cancer cells travel a distance away from the originated site to induce secondary malignant growths.

Anti-metastasis is an action in which substance or substances are used including herbal medicine to stop the cancer cell to infect other healthy tissues a distance away from the primary tumor. 

Most cancer drugs used in conventional medicine with the ability to block the migration of cancer cells are considered process antimetastatic activity.

In other words, anti-metastasis drugs are agents that interfere with all modes of cancer cell migration, compared to conventional cytostatic drugs involved in blocking cancer cell proliferation. 

Angiogenesis is the process by stimulating the growth of new blood vessels from preexisting blood vessels used by the tumor to obtain nutrient in facilitating cancer proliferation.

Anti-angiogenic activity is an action in which substances such as drugs and herbal medicine are used to stop tumors from growing their own blood vessels.

Conventionally, medicines that block the block vascular endothelial growth factor (VEGF) from attaching to the receptors on the cells that line the blood vessels. such as bevacizumab (Avastin). Bevacizumab is considered anti-angiogenic drugs.

Believe it or not, as of today, there is no anti-metastatic drug on the market,  even over 90 percent of cancer deaths today are due to metastasis formation. Dr. Stock AM, the lead scientist in the examined the targets for anti-metastatic drug development, wrote, "Tumor cell migration is the essential prerequisite for invasion and metastasis formation. It is regulated by signal substances in terms of the grade of activity and in terms of direction (chemotaxis)".

And, "Moreover we provide with the example of beta-blockers, how established drugs in other indications are possibly effective and can be co-opted as such anti-metastatics".

The cucumber plant is a species of Cucumis Sativus, belongs to the family Cucurbitaceae and native to Western Asia. It is a creeping vine with roots in the ground and grows up with the support of frames.

Scientists in the urgency to find the natural compound for the treatment of cancer examined the effect of Cucurbitacin B (CuB), a plant triterpenoid found abundantly in cucumber against the metastatic and angiogenic potential of breast cancer cells.

During the experiment, CuB showed significant activity in the inhibition of cellular proliferation and induction of apoptosis in the tested cancer cells in a time- and dose-dependent manner.

Furthermore, at the sub-IC50 concentrations, injection of CuB inhibited the migratory and invasive potential of highly metastatic breast cancer MDA-MB-231 and 4T1 cells.

In HUVECs, administration of CubB also inhibited migratory, invasive and tube-forming capacities.

In chick embryo chorioallantoic membrane, CuB exerted a strong anti-angiogenic effect in the prevention of new blood vessels.

According to the tested assay, the efficacy of Cub antimetastatic and angiogenic properties was attributed to the blocking of the matrix and proteins (VEGF/FAK/MMP-9) in signaling the development of new blood vessels from the existing vessels to induce cancer cells proliferation.

Additionally, the anti-angiogenesis was also evidenced by the decreased protein CD31 associated with more than 90% of angiosarcomas.

Dr. Sinha S, the lead scientists said, "Collectively, our findings suggest that CuB inhibited breast cancer metastasis and angiogenesis, at least in part, through the downregulation of VEGF/FAK/MMP-9 signaling".

In non-small cell lung cancer (NSCLC) both in vitro and in vivo, at nanomolar concentrations injection of CuB demonstrated a strong anti-migratory and anti-invasive ability against metastatic NSCLC by blocking the migratory, invasive and tube-forming capacities.

The efficacy of the tested compound in this experiment inhibited metastasis and angiogenesis was attributable to the suppression of proteins (Wnt/β-catenin) associated with pass signals into a cell through cell surface receptors to induce cell proliferation and formation of new blood vessels.

Taken altogether, cucumber processed a high amount of CuB may be considered supplements for the prevention and treatment of cancer, pending to the confirmation of the larger sample size and multicenter human study.

Intake of CuB in the form of supplement should be taken with extreme care to prevent overdose acute liver toxicity.

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Author Biography
Kyle J. Norton (Scholar, Master of Nutrition, All right reserved)

Health article writer and researcher; Over 10.000 articles and research papers have been written and published online, including worldwide health, ezine articles, article base, health blogs, self-growth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bioscience, ISSN 0975-6299.

(1) Cucurbitacin B inhibits breast cancer metastasis and angiogenesis through VEGF-mediated suppression of FAK/MMP-9 signaling axis by Sinha S1, Khan S1, Shukla S1, Lakra AD1, Kumar S2, Das G3, Maurya R2, Meeran SM. (PubMed)
(2) Cucurbitacin B inhibits the stemness and metastatic abilities of NSCLC via downregulation of canonical Wnt/β-catenin signaling axis by Shukla S1, Sinha S1, Khan S1, Kumar S2, Singh K3, Mitra K3, Maurya R2, Meeran SM. (PubMed)
(3) Targets for anti-metastatic drug development by Stock AM1, Troost G, Niggemann B, Zänker KS, Entschladen F. (PubMed)

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