The Nasdaq Biotech Index and the S&P Healthcare index posted their biggest daily percentage losses in about a month, after disappointing news from several companies including Amgen. The biotech index shed 4.1 percent and the healthcare index lost 1.8 percent.

The benchmark S&P 500 index hit a record intraday high before reversing course to close lower.

MSCI's all-country world stock index also touched an intraday record high.

European shares closed up about 1 percent after Greek Prime Minister Alexis Tsipras reshuffled the team handling the talks with European and International Monetary Fund lenders. Concerns over Greece have mounted since the country looks set to run out of cash in coming weeks.

"At the margin, this increases the hope for some positive developments from the Greece-EU debt negotiations," said Omer Esiner, chief market analyst at Commonwealth Foreign Exchange in Washington.

Market participants awaited the release of Apple's quarterly results after the close of U.S. trading. Apple, the most valuable publicly traded U.S. company, closed up 1.8 percent at $132.65.

Apple reported a 27 percent jump in quarterly revenue and said it raised its share repurchase program by $50 billion.

Investors were also cautious ahead of the Federal Reserve's two-day policy meeting that ends on Wednesday.

The Dow Jones industrial average closed down 42.17 points, or 0.23 percent, at 18,037.97. The S&P 500 closed down 8.77 points, or 0.41 percent, at 2,108.92. The Nasdaq Composite closed down 31.84 points, or 0.63 percent, at 5,060.25.

MSCI's all-country world stock index, which tracks shares in 45 countries, was last up 0.64 point, or 0.14 percent, at 442.21 after earlier hitting a record high of 443.98. A rise in Chinese shares to seven-year highs contributed to gains.

The pan-European FTSEurofirst 300 index closed up 0.97 percent at 1,642.69.

The euro hit $1.09270, its highest level against the dollar since April 7, on optimism over Greece's prospects for progress in talks with lenders after the reshuffle of the country's negotiating team. It later pared gains to trade up about 0.1 percent

Benchmark U.S. Treasuries prices were mostly flat, with traders reluctant to make big bets ahead of the Fed meeting. The meeting will be watched for signs of how soon the central bank will hike rates from rock-bottom levels, though the expectation is for little news out of this Fed gathering.

"It feels directionless. No one is expecting the Fed to do anything," said Gene Tannuzzo, portfolio manager at Columbia Management in Minneapolis.

Oil prices fell, with ample global supply keeping market participants cautious after prices reached 2015 peaks last week. U.S. crude settled down 16 cents at $56.99 per barrel; Brent settled down 45 cents at $64.83 a barrel.

Gold marked its biggest one-day rise since January as some dealers scrambled to cover short positions and the May options expiry triggered more buying. U.S. gold futures for June delivery settled up 2.4 percent, at $1,203.20 an ounce.

(Additional reporting by Robert Gibbons, Gertrude Chavez-Dreyfuss and Richard Leong in New York; Editing by Nick Zieminski, Bernadette Baum and Leslie Adler)

By Sam Forgione