In Vitro Enhancement of Doxorubicin Genotoxic Activities and Interference with Cell Cycle Delay by Plumbago indica Root Ethanolic Extract in Human Lymphocytes
Treetip Ratanavalachai PhD*, Sumon Thitiorul MS**, Sermkiat Tanuchit MS***, Arunporn Itharat PhD****, Intouch Sakpakdeejaroen MS****
Affiliation : * Division of Biochemistry, Faculty of Medicine, Thammasat University, Pathumthani, Thailand ** Division of Anatomy, Faculty of Medicine, Thammasat University, Pathumthani, Thailand *** Research Center, Faculty of Medicine, Thammasat University, Pathumthani, Thailand **** Division of Applied Thai Traditional medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand
Background : Combinations of modern medicines with herbal medicines are being developed for more effectiveness. Data on
the safety and drug-herb interactions are needed to be clarified. Ethanolic extract of Plumbago indica root (EEPIR) is
medicinally used for cancer treatment in Asian traditional medicine. However, its mechanism of action is still inconclusive.
Our previous study demonstrated that EEPIR was genotoxic and induced cell cycle delay in human lymphocytes in vitro.
Objective : To investigate genotoxic potency and interference with cell cycle of EEPIR in combination with doxorubicin (DXR),
a standard chemotherapeutic agent, in human lymphocytes by in vitro sister chromatid exchange (SCE) assay.
Material and Method: Human lymphocytes were pretreated with EEPIR at 6.25-100 mcg/ml followed by DXR (0.1 mcg/ml).
SCE levels and cell cycle kinetics were evaluated.
Results : EEPIR pretreatments (6.5-50 mcg/ml) significantly enhanced genetic damage induced by DXR (p<0.05). Delaying of
the cell cycle was detected and related to EEPIR concentration. EEPIR at 100 mcg/ml, on the contrary, did not enhance DXR-
induced genotoxicity but tended to lower genotoxicity compared to DXR treatment alone. It significantly delayed cell cycle the
most (p<0.05).
Conclusion : EEPIR pretreatments at proper doses enhanced genotoxic damage induced by DXR in human lymphocytes.
Delaying cell cycle by EEPIR could lower that potency. Usage of EEPIR, therefore, should be adjusted for safety. Combination
of EEPIR with DXR might be useful for more efficient cancer treatment with less DXR toxicity. Further in vivo study is needed
to support this in vitro evidence.
Keywords : Plumbago indica root, Doxorubicin, Cell cycle, Sister chromatid exchange, Human lymphocytes, Genotoxicity
