Plumbagin, A Plant Naphthoquinone with Antitumor and Radiomodifying Properties

Abstract

The tumor inhibitory and radiomodifying effects of plumbagin (Pl), a naphthoquinone isolated from Plumbago rosea, on mouse Ehrlich ascites carcinoma was studied. Tumor response was assessed by increase in life span (% ILS) and animal survival at 120 days. The acute LD 50 of plumbagin in normal mice was 9.4 mg/kg body weight. Single doses from 2 to 6 mg/kg Pl, given intraperitoneally (i.p.), produced inhibition of exponentially growing tumors. However, increases in dose above 3 mg/kg did not increase 120 day survival significantly over that produced by 3 mg/kg. Multiple dose treatment, starting from 24 h after tumor cell inoculation, showed that a total dose of 9 mg/kg, administered in three fractions of 3 mg/kg, once daily, gave the maximum %ILS and tumor free survival. Combination of radiation (RT, 7.5 Gy to the abdomen) after the first Pl dose (1-3mg/kg/fraction) synergistically increased mouse survival at 120 days. The tumor inhibitory effect was less pronounced when treatment was started at more advanced tumor stages, but combination of low dose fractions (2.5 or 3 mg/kg/fraction) with RT enhanced the %ILS and animal survival. Higher dose fractions in combination with radiation were not tolerated by the mice. DNA appears to be the likely target of Pl cytotoxicity; the mechanism of interaction of Pl + RT in enhancing tumor response is not clear.

Aegle marmelos (L.) CORREA Inhibits the Proliferation of Transplanted Ehrlich Ascites Carcinoma in Mice

“…Similar observations have been reported earlier for other plant extracts like Withania somnifera and Plumbago rosea. 33,34) From our study it is clear that AME inhibited the growth of EAC in the mice. The optimum non-toxic dose of 400 mg/kg was 1/5.6th of the LD 50 (2250 mg/kg) dose and the non-toxic nature of this drug may lie in its composite status.…”

“…The studies of the anticancer activity of plants at different stages of tumor development are scanty, however, withaferin A from Withania somnifera and plumbagin, from Plumbago rosea have been reported to inhibit EAC growth when administered in mid stages. 32,33) In conventional chemotherapy, it is important to know a drug's efficacy through oral routes as this is most convenient and does not require medical intervention in the cancer treatment; therefore, the drug was administered orally at two doses (400 or 800 mg/kg) apart from the intraperitoneal route. Our results show that the best antineoplastic action of AME was obtained when the drug was administered intraperitoneally, while the oral route was not as effective as the intraperitoneal route.…”

Enhancement of Radiation Effect by <i>Aphanamixis polystachya</i> in Mice Transplanted with Ehrlich Ascites Carcinoma

“…Similarly, phytochemicals like withaferin and plumbagin, isolated from Withania somnifera and Plumbago rosea have been reported to enhance the antitumor effect of radiation in EAC bearing mice. [47][48][49][50] The optimum dose of 50 mg/kg body wt APE in conjunction with 6 Gy irradiation has been found to be most effective while the other higher doses of APE did not enhance the radiation effect further. This effect may be attributed to the elevation of radiation-induced free radicals by APE.…”

“…The agents that deplete GSH, such as N-ethylmaleamide, bromobenzene, allyl alcohol, buthionine sulfoxamine and diethyl maleate, increase the radiation effect. 51,[53][54][55][57][58][59] The lipid peroxidation is another important event related to cell death and has been reported to cause severe impairment of membrane function through increased membrane permeability and membrane protein oxidation, DNA damage, cytotoxicity and eventually cell death. [60][61][62][63] The increased LPx may have also contributed to the higher tumor regression in the APEϩirradiation group.…”

“…12) Plumbagin, derived from the plant Plumbago zeylanica, has been reported to enhance the effect of radiation in mice bearing sarcoma S180 and Ehrlich ascites carcinoma. 13) Aphanamixis polystachya WALL & PARKER (Amoora rohituka (RoXB.) WIGHT & ARN.…”