Oral cancer is a subset of head and neck cancer. There are various types of oral cancers, including cancer of the periodontal ligament (PDL) and osteosarcoma (OS) of jawbones. In South Asian countries, the major cause of oral cancer is reported to be chewing paan, or betel leaf daubed with slaked lime paste and areca nut. To investigate how paan may contribute to the onset of cancer, we evaluated how treating cells with areca nut extract, betel leaf extract, or lime (better known as calcium hydroxide) affected cell proliferation and cell death. Two oral cell lines were treated with solutions of areca nut, young betel leaf, old betel leaf, and lime, either individually or in combination, and we evaluated cell survival and cell growth. While treatment with old betal leaf alone caused marginal slowing of cell growth of both PDL and OS cell lines (12 ± 4% and 10 ± 10%, respectively), effects of young betal leaf and lime on cell growth were minor. Treatment with areca nut caused no significant change in PDL (10 ± 10%), but an increase in cell number for OS (37 ± 19%). Extract combinations of either young or old betal leaf with areca nut and lime resulted in increased cell proliferation of PDL and OS. These initial results indicate that the enhancement of cell growth by areca nut can overcome potential growth inhibition by betal leaf, suggesting that areca nut may promote cell growth. These data warrant further investigation of the effect of areca nut exposure on the onset of oral cancer in humans.