Therapeutic potential of gambogic acid, a caged xanthone, to target cancer

Banik, Kishore; Harsha, Choudhary; Bordoloi, Devivasha; Sailo, Bethsebie Lalduhsaki; Sethi, Gautam; Leong, Hin Chong; Arfuso, Frank; Mishra, Srishti; Wang, Lingzhi; Kumar, Alan Prem; Kunnumakkara, Ajaikumar B.

doi:10.1016/j.canlet.2017.12.014

Cited by 129 publications

(78 citation statements)

References 119 publications

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“…The main reason for this is an adaptation of the cancer cells to conventional chemotherapy drugs, resulting in relapses, metastasis and death. For this reason, there is a huge necessity to develop pharmacologically-safe and relatively inexpensive anti-tumor agents as potential adjunctive treatments to enhance the overall treatment response of patients with CRC [6,7].…”

Section: Introductionmentioning

confidence: 99%

Calebin A Potentiates the Effect of 5-FU and TNF-β (Lymphotoxin α) against Human Colorectal Cancer Cells: Potential Role of NF-κB

Buhrmann

Kunnumakkara

Popper

et al. 2020

IJMS

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Objective: The majority of chemotherapeutic agents stimulate NF-κB signaling that mediates cell survival, proliferation and metastasis. The natural turmeric non-curcuminoid derivate Calebin A has been shown to suppress cell growth, invasion and colony formation in colorectal cancer cells (CRC) by suppression of NF-κB signaling. Therefore, we hypothesized here that Calebin A might chemosensitize the TNF-β-treated tumor cells and potentiates the effect of 5-Fluorouracil (5-FU) in advanced CRC. Materials and Methods: CRC cells (HCT116) and their clonogenic 5-FU chemoresistant counterparts (HCT116R) were cultured in monolayer or alginate-based 3D tumor environment culture and were treated with/without Calebin A, TNF-β, 5-FU, BMS-345541 and DTT (dithiothreitol). Results: The results showed that TNF-β increased proliferation, invasion and resistance to apoptosis in chemoresistant CRC cells. Pretreatment with Calebin A significantly chemosensitized HCT116R to 5-FU and inhibited the TNF-β-induced enhanced efforts for survival, invasion and anti-apoptotic effects. We found further that Calebin A significantly suppressed TNF-β-induced phosphorylation and nuclear translocation of p65-NF-κB, similar to BMS-345541 (specific IKK inhibitor) and NF-κB-induced tumor-promoting biomarkers (NF-κB, β1-Integrin, MMP-9, CXCR4, Ki67). This was associated with increased apoptosis in HCT116 and HCT116R cells. Furthermore, blocking of p65-NF-κB stimulation by Calebin A was imparted through the downmodulation of p65-NF-κB binding to the DNA and this suppression was turned by DTT. Conclusion: Our findings indicate, for the first time, that Calebin A chemosensitizes human CRC cells to chemotherapy by targeting of the p65-NF-κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Calebin A Potentiates the Effect of 5-FU and TNF-β (Lymphotoxin α) against Human Colorectal Cancer Cells: Potential Role of NF-κB

Buhrmann

Kunnumakkara

Popper

et al. 2020

IJMS

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“…The significant advancements made in the past few decades for unravelling the molecular causes of cancer have led to the development of numerous treatment modalities including surgery, radiation, and chemotherapy, but the disease burden still remains a challenge [2,3,4,5,6,7]. On the other hand, these chemotherapeutic agents are also associated with adverse side effects like vomiting, hyper tension, cardiovascular diseases, renal dysfunction and bone marrow destruction along with the development of chemoresistance, which further obscures the treatment procedures and ultimately leads to cancer progression and recurrence [8,9,10,11,12,13,14,15,16,17,18]. Therefore, finding a remedy with minimal side effects, cost effectiveness, easy accessibility and high efficiency is of paramount importance for the effective treatment and management of this outrageous disease.…”

Section: Introductionmentioning

confidence: 99%

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

Ranaware¹,

Banik

Deshpande³

et al. 2018

IJMS

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135

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The past few decades have witnessed widespread research to challenge carcinogenesis; however, it remains one of the most important health concerns with the worst prognosis and diagnosis. Increasing lines of evidence clearly show that the rate of cancer incidence will increase in future and will create global havoc, designating it as an epidemic. Conventional chemotherapeutics and treatment with synthetic disciplines are often associated with adverse side effects and development of chemoresistance. Thus, discovering novel economic and patient friendly drugs that are safe and efficacious is warranted. Several natural compounds have proved their potential against this dreadful disease so far. Magnolol is a hydroxylated biphenyl isolated from the root and stem bark of Magnolia tree. Magnolol can efficiently prevent or inhibit the growth of various cancers originating from different organs such as brain, breast, cervical, colon, liver, lung, prostate, skin, etc. Considering these perspectives, the current review primarily focuses on the fascinating role of magnolol against various types of cancers, and the source and chemistry of magnolol and the molecular mechanism underlying the targets of magnolol are discussed. This review proposes magnolol as a suitable candidate that can be appropriately designed and established into a potent anti-cancer drug.

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“…Further, increasing lines of evidence clearly imply that more than 70% of the current drugs are of natural origin. [245][246][247] Notably, a vast majority of world's population relies on plants for their primary healthcare. 245 Reports suggest that people of Southeast Asian countries possess lower risk of developing colon, gastrointestinal, prostate, breast, and some other cancers due to their dietary habits as dietary constituents are considered to offer protection against diverse cancers.…”

Section: Natural Therapiesmentioning

confidence: 99%

Cancer drug development: The missing links

Kunnumakkara

Bordoloi

Sailo

et al. 2019

Exp Biol Med (Maywood)

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Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.

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Therapeutic potential of gambogic acid, a caged xanthone, to target cancer

Cited by 129 publications

References 119 publications

Calebin A Potentiates the Effect of 5-FU and TNF-β (Lymphotoxin α) against Human Colorectal Cancer Cells: Potential Role of NF-κB

Calebin A Potentiates the Effect of 5-FU and TNF-β (Lymphotoxin α) against Human Colorectal Cancer Cells: Potential Role of NF-κB

Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment of Cancer

Cancer drug development: The missing links

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