South Asian Medicinal Compounds as Modulators of Resistance to Chemotherapy and Radiotherapy

Abstract

Cancer is a hyperproliferative disorder that involves transformation, dysregulation of apoptosis, proliferation, invasion, angiogenesis and metastasis. During the last 30 years, extensive research has revealed much about the biology of cancer. Chemotherapy and radiotherapy are the mainstays of cancer treatment, particularly for patients who do not respond to surgical resection. However, cancer treatment with drugs or radiation is seriously limited by chemoresistance and radioresistance. Various approaches and strategies are employed to overcome resistance to chemotherapy and radiation treatment. Many plant-derived phytochemicals have been investigated for their chemo- and radio-sensitizing properties. The peoples of South Asian countries such as India, Pakistan, Sri Lanka, Nepal, Bangladesh and Bhutan have a large number of medicinal plants from which they produce various pharmacologically potent secondary metabolites. The medicinal properties of these compounds have been extensively investigated and many of them have been found to sensitize cancer cells to chemo- and radio-therapy. This review focuses on the role of South Asian medicinal compounds in chemo- and radio-sensitizing properties in drug- and radio-resistant cancer cells. Also discussed is the role of South Asian medicinal plants in protecting normal cells from radiation, which may be useful during radiotherapy of tumors to spare surrounding normal cells.

Keywords: ABC transporter; South Asian plants; chemoresistance; phytochemicals; radioresistance.

Figure 1

Chemical structure of selected active compounds derived from South Asian Medicinal Plants.

Figure 2

Selected targets of South Asian phytochemicals linked to chemosensitization. The indicated compounds in colored boxes interact with cell surface ABC transporters such as P-gp, ABCG2, and receptor tyrosine kinases including TRIAL-R, FLT3, KIT, VEGFR and EGFR. Some of the medicinal compounds also interact with intracellular tyrosine kinases (BCR-ABL kinase). The dashed lines indicate that the phytochemicals inhibit ABC drug transporters such as P-gp and ABCG2 resulting in chemosensitization. The solid lines depict inhibition of targets such as KIT and FLT3 resulting in chemosensitization.

Figure 3

Selected targets of South Asian phytochemicals linked to radiosensitization. Exposure to ionizing radiation leads to activation of several transcription factors, expression of numerous cytokines, adhesion molecules, prostaglandins and enzymes that promote radioresistance. The upward black arrows depict up-regulation of indicated transcription factors. Solid lines indicate South Asian medicinal compounds inhibiting transcription potential of pro-inflammatory transcription factors. The curved green arrows indicate downregulation of expression of proinflammatory cytokines and enzymes involved in radioresistance by South Asian medicinal compounds. Dotted lines indicate South Asian medicinal compounds involved in the inhibition of prosurvival, cell proliferation, growth, invasion, angiogenesis and metastasis through various mechanisms.