Physapubescin, a predominant steroidal lactone, can decrease HIF-2α expression and cause death receptor 5 (DR5) upregulation, caspase-8 and -3 activation, and cleavage of poly (ADP-ribose) polymerase (PARP), which serves as a novel proapoptotic agent targeting VHL-null RCC cells [86]. The gene discussed is CASP8; the disease is renal cell carcinoma.